Associations of parental and perinatal factors with subsequent risk of stress-related disorders: a nationwide cohort study with sibling comparison

Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973–2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity ≥4, mothers with BMI ≥ 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32–36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06–1.12] and sibling analyses (HR 1.10, 95% CI 1.02–1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.

Prenatal and Perinatal Factors Associated with Pediatric Autism Spectrum Disorder in East China

Background Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by persistent challenges in social communication and interaction and restricted/repetitive patterns of behavior, interests or activities. An increasing number of studies have revealed that environmental exposure is a potential risk factor for ASD. The relationship between prenatal and perinatal risk factors and ASD has rarely been studied in large samples in China. Therefore, in this study, we compared children with ASD with typical developing (TD) children to assess the ASD-associated prenatal and perinatal risk factors and provide effective information for ASD prevention. Methods A case-control study of 709 children with autism spectrum disorder (ASD) and 709 gender-matched children with typical development was conducted to investigate the prenatal and perinatal risk factors of children with ASD compared with children with typical development ( TD). Through a self-developed general information questionnaire, the basic information (name, age, gender), prenatal factors (parents’ age at the child’s birth, parents’ education levels, use of assisted reproductive technology, history of miscarriage, gestational diabetes mellitus, gestational hypertension), and perinatal factors (delivery mode, full-term birth, parity, birth weight) of the children in the two groups were examined. Results The prenatal and perinatal factors of the groups were submitted to univariate analysis, the parent’s age at childbirth, education level, history of miscarriage, use of ART, pregnancy-induced hypertension, and GDM differed significantly between the two groups (P<0.05), and that among perinatal factors, infant parity and maturity also differed significantly between the two groups (P<0.05). These statistically significant factors were included in a binary logistic regression model. The results showed that the prenatal factors of young maternal age at the child’s birth (≤24 years vs 25-29 years, OR=2.408,95%CI:1.335~4.345), old paternal age at the childbirth(≥45years vs≤24years, OR=4.744, 95%CI:1.281~17.570 ), pregnancy induced hypertension (OR=6.178, 95%CI:2.311~16.517) and GDM(OR=0.220,95%CI:0.149~0.324), the perinatal factors of preterm birth(OR=4.434, 95%CI:2.872~6.846) and non-firstborn child(OR=1.387, 95%CI:1.029~1.869) are likely risk factors for ASD. Conclusion We show that some prenatal and perinatal factors are associated with a high prevalence of ASD in children.

Role of Bifidobacteria on Infant Health

Bifidobacteria are among the predominant microorganisms during infancy, being a dominant microbial group in the healthy breastfed infant and playing a crucial role in newborns and infant development. Not only the levels of the Bifidobacterium genus but also the profile and quantity of the different bifidobacterial species have been demonstrated to be of relevance to infant health. Although no definitive proof is available on the causal association, reduced levels of bifidobacteria are perhaps the most frequently observed alteration of the intestinal microbiota in infant diseases. Moreover, Bifidobacterium strains have been extensively studied by their probiotic attributes. This review compiles the available information about bifidobacterial composition and function since the beginning of life, describing different perinatal factors affecting them, and their implications on different health alterations in infancy. In addition, this review gathers exhaustive information about pre-clinical and clinical studies with Bifidobacterium strains as probiotics in neonates.

Obesity and Cardiometabolic Risk Factors: From Childhood to Adulthood

Obesity has become a major epidemic in the 21st century. It increases the risk of dyslipidemia, hypertension, and type 2 diabetes, which are known cardiometabolic risk factors and components of the metabolic syndrome. Although overt cardiovascular (CV) diseases such as stroke or myocardial infarction are the domain of adulthood, it is evident that the CV continuum begins very early in life. Recognition of risk factors and early stages of CV damage, at a time when these processes are still reversible, and the development of prevention strategies are major pillars in reducing CV morbidity and mortality in the general population. In this review, we will discuss the role of well-known but also novel risk factors linking obesity and increased CV risk from prenatal age to adulthood, including the role of perinatal factors, diet, nutrigenomics, and nutri-epigenetics, hyperuricemia, dyslipidemia, hypertension, and cardiorespiratory fitness. The importance of ‘tracking’ of these risk factors on adult CV health is highlighted and the economic impact of childhood obesity as well as preventive strategies are discussed.

Characteristics Associated with Tumor Development in Individuals Diagnosed with Beckwith–Wiedemann Spectrum: Novel Tumor-(epi)Genotype-Phenotype Associations in the BWSp Population

Beckwith–Wiedemann Spectrum (BWSp) is the most common epigenetic childhood cancer predisposition disorder. BWSp is caused by (epi)genetic changes affecting the BWS critical region on chromosome 11p15. Clinically, BWSp represents complex molecular and phenotypic heterogeneity resulting in a range of presentations from Classic BWS to milder features. The previously reported tumor risk based on Classic BWS cohorts is 8–10% and routine tumor screening has been recommended. This work investigated the tumor risk and correlation with phenotype within a cohort of patients from Classic BWS to BWSp using a mixed-methods approach to explore phenotype and epigenotype profiles associated with tumor development through statistical analyses with post-hoc retrospective case series review. We demonstrated that tumor risk across BWSp differs from Classic BWS and that certain phenotypic features are associated with specific epigenetic causes; nephromegaly and/or hyperinsulinism appear associated with cancer in some patients. We also demonstrated that prenatal and perinatal factors that are not currently part of the BWSp classification may factor into tumor risk. Additionally, blood testing results are not necessarily synonymous with tissue testing results. Together, it appears that the current understanding from Classic BWS of (epi)genetics and phenotype correlations with tumors is not represented in the BWSp. Further study is needed in this complex population.

Early nutrition and later excess adiposity during childhood. A narrative review

BACKGROUND: Studies on childhood obesity mainly focus on the genetic component and on the lifestyle that may be associated with the development of obesity. However, the study of perinatal factors in their programming effect towards future obesity in children or adults is somewhat more recent and there are still mechanisms to be disentangled. SUMMARY: In this narrative review, a comprehensive route based on the influence of some early factors in life in the contribution to later obesity development is presented. Maternal pre-pregnancy BMI and gestational weight gain has been pointed out as independent determinants of infant later adiposity. Lifestyle interventions could have an impact on pregnant mothers throught epigenetic mechanisms capable of redirecting the genetic expression of their children towards a future healthy weight and body composition and dietary-related microbiome modifications in mothers and newborn might also be related. After birth, infant feeding during the first months of life is directly associated with its body composition and nutritional status. From this point of view, all the expert committees in the world are committed to promote exclusive breastfeeding up to 6 months of age, and to continue at least until the first year of life together with complementary feeding based on healthy dietary patterns such as Mediterranean Diet. KEY MESSAGES: To develop future effective programs to tackle early obesity, is necessary not only by controlling lifestyle behaviors like infant feeding but also understanding the role of other mechanisms like the effect of perinatal factors such as maternal diet during pregnancy, epigenetics or microbiome.